The goal of this study is to analyze the biological significance of the interferon system in human immunodeficiency syndrome (AIDS). In this proposal, we wish to analyze the roles which interferons play in the life cycle and pathophysiology of HIV infection and establish the efficacy of interferon therapy in AIDS disease. We have shown previously that interferon induced inhibition of murine leukemia virus (MuLV) replication occurs at the level of virus assembly and that interferon treatment leads to a formation of non-infectious particles. Our recent results show that the HIV infection in both T-cells and monocytes is sensitive to the antiviral effect of interferon. It may be anticipated that the interferon-induced block of HIV replication may not be completely identical to that seen with MuLV since the HIV replication cycle includes unique steps not seen in MuLV. In addition, we have shown recently that the infection with viruses of Herpes virus group activates the transcription of HIV and identified both the inducible sequence in the HIV-LTR and the transactivating viral protein. The present proposal is an extension of these studies and will focus on the following questions: 1) what is the role of interferon in HIV replication and HIV induced AIDS symptoms; 2) at what level of HIV replicative cycle does interferon block occur 3) can interferon inhibit HIV activation by heterologous viruses; and 4) can we, by using concepts of gene therapy, target interferon synthesis to the focus of HIV infection and thus, eliminate the toxic effects of interferon that are associated with long-term application of exogenous interferon. We believe that results of this study will allow us to evaluate in molecular terms the complex role of interferon system in human retroviral infection and will also provide a firm foundaton for the use of interferon therapy in of HIV infection in man.